Deletion of Oncomodulin Gives Rise to Early Progressive Cochlear Dysfunction in C57 and CBA Mice.

Ca2+ signaling is a major contributor to sensory hair cell function in the cochlea. Oncomodulin (OCM) is a Ca2+ binding protein (CaBP) preferentially expressed in outer hair cells (OHCs) of the cochlea and few other specialized cell types. Here, we expand on our previous reports and show that OCM delays hearing loss in mice of two different genetic backgrounds: CBA/CaJ and C57Bl/6J. In both backgrounds, genetic disruption of Ocm leads to early progressive hearing loss as measured by auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE). In both strains, loss of Ocm reduced hearing across lifetime (hearing span) by more than 50% relative to wild type (WT). Even though the two WT strains have very different hearing spans, OCM plays a considerable and similar role within their genetic environment to regulate hearing function. The accelerated age-related hearing loss (ARHL) of the Ocm KO illustrates the importance of Ca2+ signaling in maintaining hearing health. Manipulation of OCM and Ca2+ signaling may reveal important clues to the systems of function/dysfunction that lead to ARHL.

The fine line of defensive medicine.

Defensive medicine is a practice that has been utilized by clinicians in efforts of preventing patient dissatisfaction and malpractice claims and may be done through either omission or commission. As much as 57% of physicians have disclosed that they practice defensive medicine. However, this practice does not necessarily prevent malpractice claims and more importantly, neither does it equate to good medical practice, with some leading to poor outcomes. Unfortunately, there is a high percentage of malpractice claims lodged against clinicians in both primary care and hospital settings. Specialists such as surgeons, obstetricians, and gynecologists face the highest claims. In particular, during the SARS CoV-2 pandemic, with new challenges and limited treatment algorithms, there is an even greater concern for possible bourgeoning claims. Counteracting defensive medicine can be accomplished through decriminalizing malpractice claims, leaving physician oversight up to state medical boards and hospital claims management committees. Additional tort reform measures must also be taken such as caps on noneconomic damages to ensure emphasis on beneficence and nonmaleficence. Once these are in place, it may well serve to increase clinician-patient trust and improve patient independence in the shared decision-making process of their treatment, allowing clinicians to practice their full scope of practice without feeling wary of potential malpractice claims.

Environmental Tuning of Homologs of the Orange Carotenoid Protein-Encoding Gene in the Cyanobacterium Fremyella diplosiphon.

The orange carotenoid protein (OCP) family of proteins are light-activated proteins that function in dissipating excess energy absorbed by accessory light-harvesting complexes, i.e., phycobilisomes (PBSs), in cyanobacteria. Some cyanobacteria contain multiple homologs of the OCP-encoding gene (ocp). Fremyella diplosiphon, a cyanobacterium studied for light-dependent regulation of PBSs during complementary chromatic acclimation (CCA), contains several OCP homologs - two full-length OCPs, three Helical Carotenoid Proteins (HCPs) with homology to the N-terminus of OCP, and one C-terminal domain-like carotenoid protein (CCP) with homology to the C-terminus of OCP. We examined whether these homologs are distinctly regulated in response to different environmental factors, which could indicate distinct functions. We observed distinct patterns of expression for some OCP, HCP, and CCP encoding genes, and have evidence that light-dependent aspects of ocp homolog expression are regulated by photoreceptor RcaE which controls CCA. RcaE-dependent transcriptional regulator RcaC is also involved in the photoregulation of some hcp genes. Apart from light, additional environmental factors associated with cellular redox regulation impact the mRNA levels of ocp homologs, including salt, cold, and disruption of electron transport. Analyses of conserved sequences in the promoters of ocp homologs were conducted to gain additional insight into regulation of these genes. Several conserved regulatory elements were found across multiple ocp homolog promoters that potentially control differential transcriptional regulation in response to a range of environmental cues. The impact of distinct environmental cues on differential accumulation of ocp homolog transcripts indicates potential functional diversification of this gene family in cyanobacteria. These genes likely enable dynamic cellular protection in response to diverse environmental stress conditions in F. diplosiphon.

Stemming the Tide of Opioid Addiction-Dramatic Reductions in Postoperative Opioid Requirements Through Preoperative Education and a Standardized Analgesic Regimen.

INTRODUCTION: Surgery is a known gateway to opioid use that may result in long-term morbidity. Given the paucity of evidence regarding the appropriate amount of postoperative opioid analgesia and variable prescribing education, we investigated prescribing habits before and after institution of a multimodal postoperative pain management protocol. MATERIALS AND METHODS: Laparoscopic appendectomies, laparoscopic cholecystectomies, inguinal hernia repairs, and umbilical hernia repairs performed at a tertiary military medical center from 01 October 2016 until 30 September 2017 were examined. Prescriptions provided at discharge, oral morphine equivalents (OME), repeat prescriptions, and demographic data were obtained. A pain management regimen emphasizing nonopioid analgesics was then formulated and implemented with patient education about expected postoperative outcomes. After implementation, procedures performed from 01 November 2017 until 28 February 2018 were then examined and analyzed. Additionally, a patient satisfaction survey was provided focusing on efficacy of postoperative pain control. RESULTS: Preprotocol, 559 patients met inclusion criteria. About 97.5% were provided an opioid prescription, but prescriptions varied widely (256 OME, standard deviation [SD] 109). Acetaminophen was prescribed often (89.5%), but nonsteroidal anti-inflammatory drug (NSAID) prescriptions were rare (14.7%). About 6.1% of patients required repeat opioid prescriptions. After implementation, 181 patients met inclusion criteria. Initial opioid prescriptions decreased 69.8% (77 OME, SD 35; P < 0.001), while repeat opioid prescriptions remained statistically unchanged (2.79%; P = 0.122). Acetaminophen prescribing rose to 96.7% (P = 0.002), and NSAID utilization increased to 71.0% (P < 0.001). Postoperative survey data were obtained in 75 patients (41.9%). About 68% stated that they did not use all of the opioids prescribed and 81% endorsed excellent or good pain control throughout their postoperative course. CONCLUSIONS: Appropriate preoperative counseling and utilization of nonopioid analgesics can dramatically reduce opioid use while maintaining high patient satisfaction. Patient-reported data suggest that even greater reductions may be possible.

Integration of a recent infection testing algorithm into HIV surveillance in Ireland: improving HIV knowledge to target prevention.

Recent infection testing algorithms (RITA) for HIV combine serological assays with epidemiological data to determine likely recent infections, indicators of ongoing transmission. In 2016, we integrated RITA into national HIV surveillance in Ireland to better inform HIV prevention interventions. We determined the avidity index (AI) of new HIV diagnoses and linked the results with data captured in the national infectious disease reporting system. RITA classified a diagnosis as recent based on an AI < 1.5, unless epidemiological criteria (CD4 count <200 cells/mm3; viral load <400 copies/ml; the presence of AIDS-defining illness; prior antiretroviral therapy use) indicated a potential false-recent result. Of 508 diagnoses in 2016, we linked 448 (88.1%) to an avidity test result. RITA classified 12.5% of diagnoses as recent, with the highest proportion (26.3%) amongst people who inject drugs. On multivariable logistic regression recent infection was more likely with a concurrent sexually transmitted infection (aOR 2.59; 95% CI 1.04-6.45). Data were incomplete for at least one RITA criterion in 48% of cases. The study demonstrated the feasibility of integrating RITA into routine surveillance and showed some ongoing HIV transmission. To improve the interpretation of RITA, further efforts are required to improve completeness of the required epidemiological data.

Patient Education and Pharmacist Consultation Influence on Nonbenzodiazepine Sedative Medication Deprescribing Success for Older Adults.

INTRODUCTION: Use of nonbenzodiazepine sedative hypnotics or "Z-drugs"-including eszopiclone, zolpidem, or zaleplon-is discouraged for older adults; however, these medications commonly are prescribed to treat insomnia in this population. We evaluated the impact of direct-to-patient education, with or without a pharmacist consultation, on Z-drug discontinuation among Kaiser Permanente Northwest members age 64 years and older. METHODS: We randomized 150 patients to usual care (UC), educational information only, or educational information and pharmacist consultation. Patients age 64 years and older who received 2 to 3 Z-drug fills in 2016 were included. Logistic regression was used to calculate odds of discontinuation at 6 months among patients who received either intervention, compared with those who received UC. RESULTS: Patients who received education only and education plus pharmacist consultation were significantly more likely to discontinue Z-drug use than those who received UC (28/50 of those who received education only and 27/49 of those who received education plus consultation vs 13/50 patients who received UC). After controlling for patient demographics, comorbidity, and antianxiety and antidepressant medication use, patients who received education only had greater odds of Z-drug discontinuation than those in the UC group (adjusted odds ratio = 4.02, 95% confidence interval = 1.66-9.77). Patients who received education and a pharmacist call also had greater odds of discontinuing use of these drugs than those in the UC group (adjusted odds ratio = 4.10, 95% confidence interval = 1.65-10.19). CONCLUSION: Patients who received direct-to-patient education with or without a pharmacist consultation were significantly more likely to discontinue Z-drug use than patients receiving UC. Providing evidence-based information about Z-drug use is an effective and low-resource method to encourage drug discontinuation.

Modeling underwater noise propagation from marine hydrokinetic power devices through a time-domain, velocity-pressure solution.

Marine hydrokinetic (MHK) devices generate electricity from the motion of tidal and ocean currents, as well as ocean waves, to provide an additional source of renewable energy available to the United States. These devices are a source of anthropogenic noise in the marine ecosystem and must meet regulatory guidelines that mandate a maximum amount of noise that may be generated. In the absence of measured levels from in situ deployments, a model for predicting the propagation of sound from an array of MHK sources in a real environment is essential. A set of coupled, linearized velocity-pressure equations in the time-domain are derived and presented in this paper, which are an alternative solution to the Helmholtz and wave equation methods traditionally employed. Discretizing these equations on a three-dimensional (3D), finite-difference grid ultimately permits a finite number of complex sources and spatially varying sound speeds, bathymetry, and bed composition. The solution to this system of equations has been parallelized in an acoustic-wave propagation package developed at Sandia National Labs, called Paracousti. This work presents the broadband sound pressure levels from a single source in two-dimensional (2D) ideal and Pekeris wave-guides and in a 3D domain with a sloping boundary. The paper concludes with demonstration of Paracousti for an array of MHK sources in a simple wave-guide.

Barriers and Facilitators to the Deprescribing of Nonbenzodiazepine Sedative Medications Among Older Adults.

INTRODUCTION: Nonbenzodiazepine sedative-hypnotic medications, or "Z-drugs," are commonly used to treat insomnia among older adults (≥ 65 years), despite a lack of evidence of long-term effectiveness and evidence linking long-term use with poor outcomes. OBJECTIVE: To understand patient and clinician barriers and facilitators to deprescribing, or discontinuation, of Z-drugs. METHODS: We conducted a qualitative interview study among older adults who received a deprescribing intervention and among their clinicians at Kaiser Permanente Northwest. Semistructured interviews explored perceived barriers and facilitators to successful deprescribing of Z-drugs. Interviews were audiorecorded with participant permission. Content was analyzed using QSR NVivo 10 software. RESULTS: From the perspectives of patients, the greatest challenges to deprescribing are factors related to their insomnia, including the need for effective treatment of their insomnia; health care system factors, including a desire for personalized approaches to care; and their own positive personal experiences with sedative medication use. From the clinician perspective, a lack of institutional structures and resources to support deprescribing, the attitudes and practices of previous clinicians, and patient-related factors such as dependence and a lack of alternatives to treat insomnia were the most important barriers to deprescribing. CONCLUSIONS: Health care systems must provide individualized care that supports patient goals for restful sleep and quality of life while also providing evidence-based care that takes patient safety into account. To accomplish this, systems must support patients and clinicians and provide a multidisciplinary approach that addresses insomnia treatment, provides patient education about sedative medication use, and supports the discontinuation process.

The Halifax Explosion a century later: Lessons for our time.

A brief historical account of the Halifax Explosion, one of North America's greatest mass urban trauma casualty events of the 20th century. This disaster, in Halifax, Nova Scotia, was the result of the cataclysmic explosion of a fully loaded World War I munitions ship on the densely waterfront of that city, resulting in nearly 2000 fatalities and 9000 injured. It remains a case study in response to disasters which overwhelm local medical capabilities.

Nutrient-extraction blender preparation reduces postprandial glucose responses from fruit juice consumption.

Although whole-fruit consumption is regarded as protective against type 2 diabetes (T2DM), conventionally prepared fruit juice is associated with increased T2DM risk, and current public health advice recommends its restriction. 'Nutrient extractor' style blenders are increasing in popularity worldwide as an alternative means of juicing fruit, but little is known about their effect on postprandial glucose levels. The current study investigated the effect of nutrient extraction on postprandial blood glucose response and glycemic index (GI) compared with a glucose control for both mixed fruit and a high GI fruit (mango). Remarkably, consumption of nutrient-extracted mixed fruit resulted in a significant lowering of the GI (32.7±8.5) compared with whole mixed fruit (66.2±8.2, P<0.05). For the high GI mango, there were no differences between nutrient-extracted and whole fruit, indicating that even for a high GI fruit the effect of nutrient extraction does not increase GI compared with the whole fruit. These findings suggest that, in contrast to conventionally prepared fruit juice, fruit juice prepared by nutrient extraction in some cases elicits a more favorable postprandial glycemic response than whole fruit and even for high GI fruits do not worsen the response. The mechanism responsible for this effect is currently unclear. However, these results suggest that fruit homogenized by nutrient extraction should be considered as a potential dietetic strategy for glycemic control.

Influence of aerobic fitness on vasoreactivity in young men.

Previous work has demonstrated a direct relationship between aerobic fitness and vasodilatory function (i.e., flow-mediated dilation; FMD); however, the relation between aerobic fitness and vasoconstrictor responsiveness (i.e., low flow-mediated constriction; L-FMC), and the overall vasoactive range (FMD + L-FMC) is unclear. PURPOSE: To test the hypothesis that L-FMC and the overall vasoactive range (FMD + L-FMC) will be related to aerobic fitness in young, healthy men. METHODS: Twenty men (age: 23 ± 5 years) were recruited, and divided evenly into a higher (HF) vs. lower (LF) aerobic fitness group, quantified via YMCA cycle ergometry (VO2 peak extrapolation), and a 3-min step test (1-min heart rate recovery). Duplex Doppler-ultrasound was used to assess brachial artery FMD and L-FMC. RESULTS: Estimated VO2 peak (HF = 55 ± 10 vs. LF = 38 ± 5 mL/kg/min) and heart rate recovery (HF = 36 ± 10 vs. LF = 25 ± 8 beats) were greater in the HF group (P < 0.05). FMD and the vasoactive range were similar between groups; however, L-FMC was significantly greater in HF (HF = -2.5 ± 1.6 vs. LF = -0.7 ± 1.8%, P < 0.05; d = 1.18). A correlational analysis revealed an inverse relationship between L-FMC and both HR recovery (r = -0.665, P < 0.01) and estimated VO2 peak (r = -0.5, P < 0.05). CONCLUSIONS: This work supports an association between L-FMC and aerobic fitness in young, healthy men. Longitudinal or interventional studies are warranted to support causality, and to distinguish whether L-FMC is more sensitive to changes in aerobic fitness than FMD.

Cost-effectiveness of population-based, community, workplace and individual policies for diabetes prevention in the UK.

AIM: To analyse the cost-effectiveness of different interventions for Type 2 diabetes prevention within a common framework. METHODS: A micro-simulation model was developed to evaluate the cost-effectiveness of a range of diabetes prevention interventions including: (1) soft drinks taxation; (2) retail policy in socially deprived areas; (3) workplace intervention; (4) community-based intervention; and (5) screening and intensive lifestyle intervention in individuals with high diabetes risk. Within the model, individuals follow metabolic trajectories (for BMI, cholesterol, systolic blood pressure and glycaemia); individuals may develop diabetes, and some may exhibit complications of diabetes and related disorders, including cardiovascular disease, and eventually die. Lifetime healthcare costs, employment costs and quality-adjusted life-years are collected for each person. RESULTS: All interventions generate more life-years and lifetime quality-adjusted life-years and reduce healthcare spending compared with doing nothing. Screening and intensive lifestyle intervention generates greatest lifetime net benefit (£37) but is costly to implement. In comparison, soft drinks taxation or retail policy generate lower net benefit (£11 and £11) but are cost-saving in a shorter time period, preferentially benefit individuals from deprived backgrounds and reduce employer costs. CONCLUSION: The model enables a wide range of diabetes prevention interventions to be evaluated according to cost-effectiveness, employment and equity impacts over the short and long term, allowing decision-makers to prioritize policies that maximize the expected benefits, as well as fulfilling other policy targets, such as addressing social inequalities.

The cost-effectiveness of changes to the care pathway used to identify depression and provide treatment amongst people with diabetes in England: a model-based economic evaluation.

BACKGROUND: Diabetes is associated with premature death and a number of serious complications. The presence of comorbid depression makes these outcomes more likely and results in increased healthcare costs. The aim of this work was to assess the health economic outcomes associated with having both diabetes and depression, and assess the cost-effectiveness of potential policy changes to improve the care pathway: improved opportunistic screening for depression, collaborative care for depression treatment, and the combination of both. METHODS: A mathematical model of the care pathways experienced by people diagnosed with type-2 diabetes in England was developed. Both an NHS perspective and wider social benefits were considered. Evidence was taken from the published literature, identified via scoping and targeted searches. RESULTS: Compared with current practice, all three policies reduced both the time spent with depression and the number of diabetes-related complications experienced. The policies were associated with an improvement in quality of life, but with an increase in health care costs. In an incremental analysis, collaborative care dominated improved opportunistic screening. The incremental cost-effectiveness ratio (ICER) for collaborative care compared with current practice was £10,798 per QALY. Compared to collaborative care, the combined policy had an ICER of £68,017 per QALY. CONCLUSIONS: Policies targeted at identifying and treating depression early in patients with diabetes may lead to reductions in diabetes related complications and depression, which in turn increase life expectancy and improve health-related quality of life. Implementing collaborative care was cost-effective based on current national guidance in England.

The impact of Type 2 diabetes prevention programmes based on risk-identification and lifestyle intervention intensity strategies: a cost-effectiveness analysis.

AIMS: To develop a cost-effectiveness model to compare Type 2 diabetes prevention programmes targeting different at-risk population subgroups with a lifestyle intervention of varying intensity. METHODS: An individual patient simulation model was constructed to simulate the development of diabetes in a representative sample of adults without diabetes from the UK population. The model incorporates trajectories for HbA1c , 2-h glucose, fasting plasma glucose, BMI, systolic blood pressure, total cholesterol and HDL cholesterol. Patients can be diagnosed with diabetes, cardiovascular disease, microvascular complications of diabetes, cancer, osteoarthritis and depression, or can die. The model collects costs and utilities over a lifetime horizon. The perspective is the UK National Health Service and personal social services. We used the model to evaluate the population-wide impact of targeting a lifestyle intervention of varying intensity to six population subgroups defined as high risk for diabetes. RESULTS: The intervention produces 0.0003 to 0.0009 incremental quality-adjusted life years and saves up to £1.04 per person in the general population, depending upon the subgroup targeted. Cost-effectiveness increases with intervention intensity. The most cost-effective options are to target individuals with HbA1c > 42 mmol/mol (6%) or with a high Finnish Diabetes Risk (FINDRISC) probability score (> 0.1). CONCLUSION: The model indicates that diabetes prevention interventions are likely to be cost-effective and may be cost-saving over a lifetime. In the model, the criteria for selecting at-risk individuals differentially impact upon diabetes and cardiovascular disease outcomes, and on the timing of benefits. These findings have implications for deciding who should be targeted for diabetes prevention interventions.

New insights into the photochemistry of carotenoid spheroidenone in light-harvesting complex 2 from the purple bacterium Rhodobacter sphaeroides.

Light-harvesting complex 2 (LH2) from the semi-aerobically grown purple phototrophic bacterium Rhodobacter sphaeroides was studied using optical (static and time-resolved) and resonance Raman spectroscopies. This antenna complex comprises bacteriochlorophyll (BChl) a and the carotenoid spheroidenone, a ketolated derivative of spheroidene. The results indicate that the spheroidenone-LH2 complex contains two spectral forms of the carotenoid: (1) a minor, "blue" form with an S2 (11B u+ ) spectral origin band at 522 nm, shifted from the position in organic media simply by the high polarizability of the binding site, and (2) the major, "red" form with the origin band at 562 nm that is associated with a pool of pigments that more strongly interact with protein residues, most likely via hydrogen bonding. Application of targeted modeling of excited-state decay pathways after carotenoid excitation suggests that the high (92%) carotenoid-to-BChl energy transfer efficiency in this LH2 system, relative to LH2 complexes binding carotenoids with comparable double-bond conjugation lengths, derives mainly from resonance energy transfer from spheroidenone S2 (11B u+ ) state to BChl a via the Qx state of the latter, accounting for 60% of the total transfer. The elevated S2 (11B u+ ) â†’ Qx transfer efficiency is apparently associated with substantially decreased energy gap (increased spectral overlap) between the virtual S2 (11B u+ ) â†’ S0 (11A g- ) carotenoid emission and Qx absorption of BChl a. This reduced energetic gap is the ultimate consequence of strong carotenoid-protein interactions, including the inferred hydrogen bonding.

Quenching Capabilities of Long-Chain Carotenoids in Light-Harvesting-2 Complexes from Rhodobacter sphaeroides with an Engineered Carotenoid Synthesis Pathway.

Six light-harvesting-2 complexes (LH2) from genetically modified strains of the purple photosynthetic bacterium Rhodobacter (Rb.) sphaeroides were studied using static and ultrafast optical methods and resonance Raman spectroscopy. These strains were engineered to incorporate carotenoids for which the number of conjugated groups (N = NC═C + NC═O) varies from 9 to 15. The Rb. sphaeroides strains incorporate their native carotenoids spheroidene (N = 10) and spheroidenone (N = 11), as well as longer-chain analogues including spirilloxanthin (N = 13) and diketospirilloxantion (N = 15) normally found in Rhodospirillum rubrum. Measurements of the properties of the carotenoid first singlet excited state (S1) in antennas from the Rb. sphaeroides set show that carotenoid-bacteriochlorophyll a (BChl a) interactions are similar to those in LH2 complexes from various other bacterial species and thus are not significantly impacted by differences in polypeptide composition. Instead, variations in carotenoid-to-BChl a energy transfer are primarily regulated by the N-determined energy of the carotenoid S1 excited state, which for long-chain (N ≥ 13) carotenoids is not involved in energy transfer. Furthermore, the role of the long-chain carotenoids switches from a light-harvesting supporter (via energy transfer to BChl a) to a quencher of the BChl a S1 excited state B850*. This quenching is manifested as a substantial (∼2-fold) reduction of the B850* lifetime and the B850* fluorescence quantum yield for LH2 housing the longest carotenoids.

Lloyd Nyhus and Rene Stoppa: preperitoneal inguinal pioneers.

A brief history of the seminal contributions of Stoppa and Nyhus to inguinal hernia surgery.

Is there a relationship between surgical case volume and mortality in congenital heart disease services? A rapid evidence review.

OBJECTIVE: To identify and synthesise the evidence on the relationship between surgical volume and patient outcomes for adults and children with congenital heart disease. DESIGN: Evidence synthesis of interventional and observational studies. DATA SOURCES: MEDLINE, EMBASE, CINAHL, Cochrane Library and Web of Science (2009-2014) and citation searching, reference lists and recommendations from stakeholders (2003-2014) were used to identify evidence. STUDY SELECTION: Quantitative observational and interventional studies with information on volume of surgical procedures and patient outcomes were included. RESULTS: 31 of the 34 papers identified (91.2%) included only paediatric patients. 25 (73.5%) investigated the relationship between volume and mortality, 7 (20.6%) mortality and other outcomes and 2 (5.9%) non-mortality outcomes only. 88.2% were from the US, 97% were multicentre studies and all were retrospective observational studies. 20 studies (58.8%) included all congenital heart disease conditions and 14 (41.2%) single conditions or procedures. No UK studies were identified. Most studies showed a relationship between volume and outcome but this relationship was not consistent. The relationship was stronger for single complex conditions or procedures. We found limited evidence about the impact of volume on non-mortality outcomes. A mixed picture emerged revealing a range of factors, in addition to volume, that influence outcome including condition severity, individual centre and surgeon effects and clinical advances over time. CONCLUSIONS: The heterogeneity of findings from observational studies suggests that, while a relationship between volume and outcome exists, this is unlikely to be a simple, independent and directly causal relationship. The effect of volume on outcome relative to the effect of other, as yet undetermined, health system factors remains a complex and unresolved research question.

An 11,000-isolate same plate/same day comparison of the 3 most widely used platforms for analyzing multidrug-resistant clinical pathogens.

Stewardship of the dwindling number of effective antibiotics relies on accurate phenotyping. We sought to conduct the first large-scale, same plate and day comparison of the 3 most widely used bacterial analyzers. A total of 11,020 multidrug-resistant clinical isolates corresponding to more than 485,000 data points were used to compare the 3 major identification and antibiotic susceptibility testing (AST) platforms. Bacterial suspensions, prepared from a single plate, were simultaneously tested on all platforms in the same laboratory. Discrepancies were derived from MIC values using 2014 interpretive guidelines. Molecular methods and manual microbroth dilution were reference standards. Most discrepancies were due to drug-organism-AST platform combination instead of individual factors. MicroScan misidentified Acinetobacter baumannii (P<0.001) and underestimated carbapenem susceptibility in Klebsiella pneumoniae. Vitek-2 and Phoenix had higher discrepancies for blaKPC-containing Enterobacteriaceae (P<0.05) and reported false susceptibilities more often. While all platforms performed according to standards, each had strengths and weaknesses for organism identification, assaying specific drug-organism combinations and inferring carbapenemase production.